Solid-Phase Organic Synthesis of Dexoxadrol Analogues
Michael Sax A and Bernhard Wünsch A B
+ Author Affiliations
- Author Affiliations
A Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhems-Universität Münster, Hittorfstrasse 58-62, D-48149 Münster, Germany.
B Correpsonding author. Email: wuensch@uni-muenster.de
Australian Journal of Chemistry 66(1) 93-97 https://doi.org/10.1071/CH12356
Submitted: 28 July 2012 Accepted: 4 September 2012 Published: 22 October 2012
Abstract
A solid-phase synthesis of dexoxadrol analogues like-13 and unlike-13 bearing an oxo group in the 4-position of the piperidine ring has been developed using aminomethyl substituted polystyrene resin as solid support. The synthesis comprises a hetero-Diels–Alder reaction of imine 7b with Danishefsky’s diene 8 in the presence of the Lewis acid Yb(OTf)3 and a conjugate reduction of the double bond of 9b with LiBHEt3 and BF3. The cleavage of the product from the solid support was performed with 1-chloroethyl chloroformate. All transformations on the solid support and additionally the cleavage reaction had to be compatible with the large and acid labile acetalic 1,3-dioxolane moiety in 2-position of the piperidine ring. The oxodexoxadrol derivative 12 was obtained in an overall yield of 17 %.
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